Idiopathic Scoliosis, Spondylolisthesis
Conditions
Keywords
opioid tolerance, hyperalgesia, scoliosis, pupillometry
Brief summary
The purpose of this study is to: 1\. Establish whether ketamine can decrease opioid consumption and modulate the onset of opioid tolerance and prevent opioid-induced hyperalgesia in pediatric subjects, ages 10 years to 18 years, undergoing posterior spinal fusion and instrumentation.
Interventions
DRUGKetamine
ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h
DRUGNormal Saline
Normal saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h
Sponsors
Julia Finkel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. The subject is 10 to 18 years of age 2. The subject's American Society of Anesthesiologists physical status is ASA 1, 2 or 3 (see appendix I) 3. The subject is scheduled for elective posterior spinal fusion and instrumentation. 4. The subject's parent/legally authorized guardian has given written informed consent to participate
Exclusion criteria
1. The subject has a history or a family (parent or sibling) history of malignant hyperthermia 2. The subject is pregnant or nursing. 3. The subject has known significant renal disorders determined by medical history, physical examination or laboratory tests 4. The subject has a known or suspected allergy to morphine, remifentanil or ketamine 5. The subject is an ASA classification of 4 or greater (See Appendix I) 6. The subject is scheduled for a surgical sub-procedure (i.e. anterior spinal fusion) 7. The subject is unable to self-administer morphine using patient-controlled analgesia (PCA) pump 8. The subject had a recent opioid exposure (within 1 month of surgery) 9. The subject is obese (body mass index \>30kg/m2) 10. The subject is planned for elective postoperative ventilation 11. The subject has a known ocular disease not permitting pupillometric examination 12. The subject has used any investigation products in the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morphine Equivalent Consumption (mg/kg) | at 24, 48, 72, 96 hours post operatively | Morphine consumption (mg/kg) was measured over time in the Ketamine group and compared to the Control (saline) group. Values are for each 24 hour time period and displayed as hours post surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sedation Score | 24, 48, 72, 96 hours post operatively | Sedation scores 0 = completely awake 1. = sleepy but responds appropriately 2. = somnolent but arouses to light stimuli 3. = asleep but responsive to deeper physical stimuli 4. = asleep and not responsive to any stimuli Values are for each 24 hour time period and displayed as hours post surgery. |
| Pain Score at Rest | 24, 48, 72, 96 hours post operatively | Patient volunteered response at rest, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery. |
| Pain Score During Cough. | 24, 48, 72, 96 hours post operatively | Patient volunteered response during a cough, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg\*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1. | 29 |
| Saline Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1. | 21 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Allergy | 1 | 0 |
| Overall Study | loss of neuromonitoring signals | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Ketamine | Saline | Total |
|---|---|---|---|
| Age, Continuous | 14 years | 14 years | 14 years |
| American Society of Anesthesiology classification ASA 1 | 13 participants | 14 participants | 27 participants |
| American Society of Anesthesiology classification ASA 2 | 15 participants | 7 participants | 22 participants |
| American Society of Anesthesiology classification ASA 3 | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 29 participants | 21 participants | 50 participants |
| Sex: Female, Male Female | 24 Participants | 14 Participants | 38 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 29 | 0 / 21 |
| serious Total, serious adverse events | 1 / 29 | 0 / 21 |
Outcome results
Primary
Morphine Equivalent Consumption (mg/kg)
Morphine consumption (mg/kg) was measured over time in the Ketamine group and compared to the Control (saline) group. Values are for each 24 hour time period and displayed as hours post surgery.
Time frame: at 24, 48, 72, 96 hours post operatively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Morphine Equivalent Consumption (mg/kg) | 24 hrs after surgery | 1.3 mg/kg | Standard Deviation 0.3 |
| Ketamine | Morphine Equivalent Consumption (mg/kg) | 48 hrs after surgery | 1.28 mg/kg | Standard Deviation 0.26 |
| Ketamine | Morphine Equivalent Consumption (mg/kg) | 72 hrs after surgery | .89 mg/kg | Standard Deviation 0.55 |
| Ketamine | Morphine Equivalent Consumption (mg/kg) | 96 hrs after surgery | .57 mg/kg | Standard Deviation 0.44 |
| Saline | Morphine Equivalent Consumption (mg/kg) | 96 hrs after surgery | .38 mg/kg | Standard Deviation 0.35 |
| Saline | Morphine Equivalent Consumption (mg/kg) | 24 hrs after surgery | 1.36 mg/kg | Standard Deviation 0.42 |
| Saline | Morphine Equivalent Consumption (mg/kg) | 72 hrs after surgery | .93 mg/kg | Standard Deviation 0.36 |
| Saline | Morphine Equivalent Consumption (mg/kg) | 48 hrs after surgery | 1.275 mg/kg | Standard Deviation 0.31 |
Secondary
Pain Score at Rest
Patient volunteered response at rest, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.
Time frame: 24, 48, 72, 96 hours post operatively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Pain Score at Rest | 24 hrs after surgery | 3.9 pain score at rest | Standard Deviation 2.1 |
| Ketamine | Pain Score at Rest | 48 hrs after surgery | 4.53 pain score at rest | Standard Deviation 1.69 |
| Ketamine | Pain Score at Rest | 72 hrs after surgery | 3.6 pain score at rest | Standard Deviation 2.3 |
| Ketamine | Pain Score at Rest | 96 hrs after surgery | 4.48 pain score at rest | Standard Deviation 2.1 |
| Saline | Pain Score at Rest | 96 hrs after surgery | 3.8 pain score at rest | Standard Deviation 1.8 |
| Saline | Pain Score at Rest | 24 hrs after surgery | 4.55 pain score at rest | Standard Deviation 2 |
| Saline | Pain Score at Rest | 72 hrs after surgery | 3.48 pain score at rest | Standard Deviation 2 |
| Saline | Pain Score at Rest | 48 hrs after surgery | 5.2 pain score at rest | Standard Deviation 2.2 |
Secondary
Pain Score During Cough.
Patient volunteered response during a cough, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.
Time frame: 24, 48, 72, 96 hours post operatively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Pain Score During Cough. | 48 hrs after surgery | 5.4 pain score at cough | Standard Deviation 2.3 |
| Ketamine | Pain Score During Cough. | 24 hrs after surgery | 4.5 pain score at cough | Standard Deviation 2.5 |
| Ketamine | Pain Score During Cough. | 72 hrs after surgery | 4.4 pain score at cough | Standard Deviation 2.3 |
| Ketamine | Pain Score During Cough. | 96 hrs after surgery | 5.15 pain score at cough | Standard Deviation 2.5 |
| Saline | Pain Score During Cough. | 96 hrs after surgery | 4.2 pain score at cough | Standard Deviation 2 |
| Saline | Pain Score During Cough. | 24 hrs after surgery | 5.1 pain score at cough | Standard Deviation 3 |
| Saline | Pain Score During Cough. | 48 hrs after surgery | 5.45 pain score at cough | Standard Deviation 2.7 |
| Saline | Pain Score During Cough. | 72 hrs after surgery | 3.7 pain score at cough | Standard Deviation 2.5 |
Secondary
Sedation Score
Sedation scores 0 = completely awake 1. = sleepy but responds appropriately 2. = somnolent but arouses to light stimuli 3. = asleep but responsive to deeper physical stimuli 4. = asleep and not responsive to any stimuli Values are for each 24 hour time period and displayed as hours post surgery.
Time frame: 24, 48, 72, 96 hours post operatively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Sedation Score | 72 hrs after surgery | .38 Sedation Score | Standard Deviation 0.45 |
| Ketamine | Sedation Score | 96 hrs after surgery | .24 Sedation Score | Standard Deviation 0.43 |
| Ketamine | Sedation Score | 24 hrs after surgery | .73 Sedation Score | Standard Deviation 0.68 |
| Ketamine | Sedation Score | 48 hrs after surgery | .62 Sedation Score | Standard Deviation 0.8 |
| Saline | Sedation Score | 48 hrs after surgery | .54 Sedation Score | Standard Deviation 0.85 |
| Saline | Sedation Score | 72 hrs after surgery | .3 Sedation Score | Standard Deviation 0.84 |
| Saline | Sedation Score | 24 hrs after surgery | .75 Sedation Score | Standard Deviation 0.73 |
| Saline | Sedation Score | 96 hrs after surgery | .21 Sedation Score | Standard Deviation 0.39 |